Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation

Chris Jopling, Eduard Sleep, Marina Raya, Mercè Martí, Angel Raya, Juan Carlos Izpisa Belmonte

Research output: Contribution to journalArticlepeer-review

1038 Scopus citations


Although mammalian hearts show almost no ability to regenerate, there is a growing initiative to determine whether existing cardiomyocytes or progenitor cells can be coaxed into eliciting a regenerative response. In contrast to mammals, several non-mammalian vertebrate species are able to regenerate their hearts, including the zebrafish, which can fully regenerate its heart after amputation of up to 20% of the ventricle. To address directly the source of newly formed cardiomyocytes during zebrafish heart regeneration, we first established a genetic strategy to trace the lineage of cardiomyocytes in the adult fish, on the basis of the Cre/lox system widely used in the mouse. Here we use this system to show that regenerated heart muscle cells are derived from the proliferation of differentiated cardiomyocytes. Furthermore, we show that proliferating cardiomyocytes undergo limited dedifferentiation characterized by the disassembly of their sarcomeric structure, detachment from one another and the expression of regulators of cell-cycle progression. Specifically, we show that the gene product of polo-like kinase 1 (plk1) is an essential component of cardiomyocyte proliferation during heart regeneration. Our data provide the first direct evidence for the source of proliferating cardiomyocytes during zebrafish heart regeneration and indicate that stem or progenitor cells are not significantly involved in this process.

Original languageEnglish (US)
Pages (from-to)606-609
Number of pages4
Issue number7288
StatePublished - Mar 25 2010
Externally publishedYes

Bibliographical note

Funding Information:
Acknowledgements We thank M. C. Fabregat, C. Rodriguez Esteban and I. Dubova for technical assistance, and A. Faucherre for constructive criticism of the manuscript. E.S. was the recipient of a pre-doctoral fellowship from the Ministry of Innovation, Universities and Enterprise (DIUE), Generalitat de Catalunya. This work was supported by grants from Fundacion Cellex, the Ipsen Foundation, the G. Harold and Leila Y. Mathers Charitable Foundation, Sanofi-Aventis, the Ministry of Science and Innovation (MICINN), CIBER, and the National Institutes of Health.

ASJC Scopus subject areas

  • General


Dive into the research topics of 'Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation'. Together they form a unique fingerprint.

Cite this